Frontline Targeted Options for EGFR-Mutated NSCLC

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Afshin Dowlati, MD, professor in the department of medicine and hematology at Case Western Reserve University and associate director for clinical research at Case Comprehensive Cancer Center, discusses the targeted therapies available for patients with EGFR-mutated late-stage non–small cell lung cancer (NSCLC).

According to Dowlati, the first choice for treating patients who have an EGFR mutation in late-stage NSCLC is osimertinib (Tagrisso), which was approved based on the phase 3 FLAURA trial (NCT02296125) for patients with metastatic NSCLC with the more common exon 19 deletions or exon 21 L858R mutations. Osimertinib was also approved for the adjuvant setting after surgery for patients with earlier-stage disease with these mutations based on the ADAURA trial (NCT02511106).

Another agent, afatinib (Gilotrif), may be used in the frontline for patients with metastatic disease for the non-resistant EGFR mutations S768I, L861Q, and/or G719X based on subset analysis of patients with durable responses with these mutations in the LUX-Lung 2 (NCT00525148), LUX-Lung 3 (NCT00949650), and LUX-Lung 6 (NCT01121393) trials.

Two other oral agents have shown efficacy in patients with EGFR exon 20 insertions, Dowlati says. Amivantamab-vmjw (Rybrevant) was approved for the first line based on the phase 1 CHRYSALIS study (NCT02609776) of patients who had progressed on platinum-based chemotherapy. Mobocertinib (Exkivity) was approved based on a phase 1/2 study (NCT02716116) of patients with locally advanced or metastatic NSCLC who had progressed on platinum-based chemotherapy.

TRANSCRIPTION:

0:08 | Our agent of choice in the frontline setting of EGFR mutations in the setting of stage IV disease, of course, is osimertinib, and that is based on randomized phase 3 clinical trials. Similarly, if we find an EGFR mutation in early-stage disease, for which the patient had surgery, osimertinib has been approved for the adjuvant treatment of these patients as well. So really, at the end of the day, our main treatment strategy is with osimertinib.

Every once in a while, we have considered the use of afatinib for patients with uncommon EGFR mutations, where there is some data on the use of afatinib for these specific, less common mutations. And for exon 20 insertion mutations within EGFR, 2 new agents have been approved for that setting as well. Mainly, amivantamab and [mobocertinib], another oral agent; they both have been approved for exon 20 insertion. So for the more common EGFR mutations, exon 19, and exon 21, osimertinib is our drug of choice. For exon 20 insertion mutations, amivantamab is a drug that we have been using. And for less common EGFR mutations, afatinib is used as well.